Relatively little is known of the role of the hypothalamus and autonomic nervous system in the regulation of short-term energy stores and metabolism of the organism. This proposal outlines a three part investigation of the CNS mechanisms and CNS-endocrine pathways important in the short term regulation of energy metabolism in rats. Part I will investigate the effects of intrahypothalamic infusions of metabolic agents (glucose, glucose antimetabolites) with and without added insulin, on physiological responses of energy regulation (glycemia, pancreatic insulin release, adrenal medullary catecholamine (C.A.) release). Part II will investigate the effects of low-level biphasic hypothalamic and peripheral autonomic electrical stimulation on pancreatic insulin release, adrenal medullary function and glycemic levels. Part III will examine the effects of pharmacological agents (alpha-, beta-adrenergic agonists-antagonists) infused-injected intrahypothalamically on these same dependent variables. It is proposed that the experimental manipulations of Parts 1-III will demonstrate (1) the existence of dual, glucose sensitive hypothalamic regions, possibly also sensitive to the catalytic actions of insulin; that (2) generate signals in response to glucose availability and (3) activate compensatory physiological responses to regulate glucose metabolism. Included in these glycoregulatory responses are those of anabolism mediated by insulin, and responses of catabolism mediated, in part, by adrenal C. A. release. The completion of this work should provide detailed information on the specific CNS-peripheral interactions in energy homeostatic mechanisms, including the specific humoral factor monitored by the organism in regulating energy levels, knowledge of the pharmacological mediation of the hypothalamic-autonomic-endocrine pathways, and an indication of the interaction of physiological-behavioral mechanisms of energy regulation in normal animals.